scholarly journals Mechanistic picture for chemo-mechanical couplings in a bacterial proton-coupled oligopeptide transporter from Streptococcus thermophilus

2020 ◽  
Author(s):  
Kalyan Immadisetty ◽  
Mahmoud Moradi
Keyword(s):  
Molecular Dynamics ◽  
Cell Membrane ◽  
Proton Transport ◽  
Structural Changes ◽  
Streptococcus Thermophilus ◽  
Md Simulations ◽  
Electrochemical Gradient ◽  
Binding Region ◽  
Conformational Switch ◽  
Sequence Identity

AbstractProton-coupled oligopeptide transporters (POTs) use the proton electrochemical gradient to transport peptides across the cell membrane. Despite the significant biological and biomedical relevance of these proteins, a detailed mechanistic picture for chemo-mechanical couplings involved in substrate/proton transport and protein structural changes is missing. We therefore performed microsecond-level molecular dynamics (MD) simulations of bacterial POT transporter PepTSt, which shares ~80% sequence identity with the human POT, PepT1, in the substrate binding region. Three different conformational states of PepTSt were simulated including, (i) occluded, apo, (ii) inward-facing, apo, and (iii) inward-facingoccluded, Leu-Ala bound. We propose that the interaction of R33 with E299 and E300 acts as a conformational switch (i.e., to trigger the conformational change from an inward-to outward-facing state) in the substrate transport. Additionally, E299 and E400 should disengage from interacting with the substrate either through protonation or through co-ordination with a cation for the substrate to get transported.

scholarly journals Ligand-induced structural changes analysis of ribose-binding protein as studied by molecular dynamics simulations

2021 ◽  
pp. 1-12
Author(s):  
Haiyan Li ◽  
Zanxia Cao ◽  
Guodong Hu ◽  
Liling Zhao ◽  
Chunling Wang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Structural Changes ◽  
Binding Protein ◽  
Network Models ◽  
Md Simulations ◽  
Protein Domain ◽  
Opening Angle ◽  
Conformation Changes ◽  
Wide Range ◽  
Ribose Binding Protein

BACKGROUND: The ribose-binding protein (RBP) from Escherichia coli is one of the representative structures of periplasmic binding proteins. Binding of ribose at the cleft between two domains causes a conformational change corresponding to a closure of two domains around the ligand. The RBP has been crystallized in the open and closed conformations. OBJECTIVE: With the complex trajectory as a control, our goal was to study the conformation changes induced by the detachment of the ligand, and the results have been revealed from two computational tools, MD simulations and elastic network models. METHODS: Molecular dynamics (MD) simulations were performed to study the conformation changes of RBP starting from the open-apo, closed-holo and closed-apo conformations. RESULTS: The evolution of the domain opening angle θ clearly indicates large structural changes. The simulations indicate that the closed states in the absence of ribose are inclined to transition to the open states and that ribose-free RBP exists in a wide range of conformations. The first three dominant principal motions derived from the closed-apo trajectories, consisting of rotating, bending and twisting motions, account for the major rearrangement of the domains from the closed to the open conformation. CONCLUSIONS: The motions showed a strong one-to-one correspondence with the slowest modes from our previous study of RBP with the anisotropic network model (ANM). The results obtained for RBP contribute to the generalization of robustness for protein domain motion studies using either the ANM or PCA for trajectories obtained from MD.

Cellular Injection Using Carbon Nanotube: A Molecular Dynamics Study

NANO ◽  
2015 ◽  
Vol 10 (02) ◽  
pp. 1550025 ◽  
Author(s):  
Seyed Hanif Mahboobi ◽  
Alireza Taheri ◽  
Hossein Nejat Pishkenari ◽  
Ali Meghdari ◽  
Mahya Hemmat
Keyword(s):  
Molecular Dynamics ◽  
Carbon Nanotube ◽  
Cell Membrane ◽  
Minimally Invasive ◽  
Lipid Bilayer ◽  
Membrane Structure ◽  
Md Simulations ◽  
Injection Process ◽  
Drug And Gene Delivery

Determination of an injection condition which is minimally invasive to the cell membrane is of great importance in drug and gene delivery. For this purpose, a series of molecular dynamics (MD) simulations are conducted to study the penetration of a carbon nanotube (CNT) into a pure POPC cell membrane under various injection velocities, CNT tilt angles and chirality parameters. The simulations are nonequilibrium and all-atom. The force and stress exerted on the nanotube, deformation of the lipid bilayer, and strain of the CNT atoms are inspected during the simulations. We found that a lower nanotube velocity results in successfully entering the membrane with minimum disruption in the CNT and the lipid bilayer, and CNT's chirality distinctly affects the results. Moreover, it is shown that the tilt angle of the CNT influences the nanotube's buckling and may result in destroying the membrane structure during the injection process.

scholarly journals Millisecond-scale molecular dynamics simulation of spike RBD structure reveals evolutionary adaption of SARS-CoV-2 to stably bind ACE2

2020 ◽  
Author(s):  
Gard Nelson ◽  
Oleksandr Buzko ◽  
Aaron Bassett ◽  
Patricia R Spilman ◽  
Kayvan Niazi ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Md Simulations ◽  
Host Cells ◽  
Dynamics Simulation ◽  
Receptor Binding Domain ◽  
Binding Region ◽  
Angiotensin Converting Enzyme 2 ◽  
Molecular Binding ◽  
Relative Affinity ◽  
Therapeutic Development

The Receptor Binding Domain (RBD) of the SARS-CoV-2 surface spike (S) protein interacts with host angiotensin converting enzyme 2 (ACE2) to gain entry to host cells and initiate infection 1-3. Detailed, accurate understanding of key interactions between S RBD and ACE2 provides critical information that may be leveraged in the development of strategies for the prevention and treatment of COVID-19. Utilizing the published sequences and cryo-EM structures of both the viral S RBD and ACE2 4,5, we performed in silico molecular dynamics (MD) simulations of free S RBD and of its interaction with ACE2 over the exceptionally long durations of 2.9 and 2 milliseconds, respectively, to elucidate the nature and relative affinity of S RBD surface residues for the ACE2 binding region. Our findings reveal that free S RBD has assumed an optimized ACE2 binding-ready conformation, incurring little entropic penalty for binding, an evolutionary adaptation that contributes to its high affinity for the receptor 6. We further identified high probability molecular binding interactions that inform both vaccine design and therapeutic development, which may include recombinant ACE2-based spike decoys 7 and/or allosteric S RBD-ACE2 binding inhibitors 8,9 to prevent or arrest infection and thus disease.

scholarly journals Geometric Analysis of Alloreactive HLAα-Helices

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Reiner Ribarics ◽  
Rudolf Karch ◽  
Nevena Ilieva ◽  
Wolfgang Schreiner
Keyword(s):  
Molecular Dynamics ◽  
T Cells ◽  
Dynamic Properties ◽  
Peptide Binding ◽  
Geometric Analysis ◽  
Md Simulations ◽  
Binding Region ◽  
Functional Elements ◽  
Mhc Molecules ◽  
Spline Models

Molecular dynamics (MD) is a valuable tool for the investigation of functional elements in biomolecules, providing information on dynamic properties and processes. Previous work by our group has characterized static geometric properties of the two MHCα-helices comprising the peptide binding region recognized by T cells. We build upon this work and used several spline models to approximate the overall shape of MHCα-helices. We applied this technique to a series of MD simulations of alloreactive MHC molecules that allowed us to capture the dynamics of MHCα-helices’ steric configurations. Here, we discuss the variability of spline models underlying the geometric analysis with varying polynomial degrees of the splines.

scholarly journals Thermodynamics, dynamics, and structure of supercritical water at extreme conditions

2020 ◽  
Vol 22 (28) ◽  
pp. 16051-16062 ◽  
Author(s):  
Tae Jun Yoon ◽  
Lara A. Patel ◽  
Taeho Ju ◽  
Matthew J. Vigil ◽  
Alp T. Findikoglu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Supercritical Water ◽  
Structural Changes ◽  
Md Simulations ◽  
Extreme Conditions ◽  
Melting Line

Molecular dynamics (MD) simulations to understand the thermodynamic, dynamic, and structural changes in supercritical water across the Frenkel line and the melting line have been performed.

scholarly journals An Overview of Molecular Dynamics Simulation for Food Products and Processes

Processes ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 119
Author(s):  
Andrea Smith ◽  
Xin Dong ◽  
Vijaya Raghavan
Keyword(s):  
Molecular Dynamics ◽  
Food Processing ◽  
Structural Changes ◽  
Food Product ◽  
Food Products ◽  
Md Simulations ◽  
Dynamics Simulation ◽  
Chicken Breast ◽  
Optimal Processing ◽  
History Of

Molecular dynamics (MD) simulation is a particularly useful technique in food processing. Normally, food processing techniques can be optimized to favor the creation of higher-quality, safer, more functional, and more nutritionally valuable food products. Modeling food processes through the application of MD simulations, namely, the Groningen Machine for Chemical Simulations (GROMACS) software package, is helpful in achieving a better understanding of the structural changes occurring at the molecular level to the biomolecules present in food products during processing. MD simulations can be applied to define the optimal processing conditions required for a given food product to achieve a desired function or state. This review presents the development history of MD simulations, provides an in-depth explanation of the concept and mechanisms employed through the running of a GROMACS simulation, and outlines certain recent applications of GROMACS MD simulations in the food industry for the modeling of proteins in food products, including peanuts, hazelnuts, cow’s milk, soybeans, egg whites, PSE chicken breast, and kiwifruit.

scholarly journals Deswelling of microfibril bundles in drying wood studied by small-angle neutron scattering and molecular dynamics

Cellulose ◽  
2021 ◽  
Author(s):  
Aleksi Zitting ◽  
Antti Paajanen ◽  
Lauri Rautkari ◽  
Paavo A. Penttilä
Keyword(s):  
Molecular Dynamics ◽  
Neutron Scattering ◽  
Small Angle ◽  
Small Angle Neutron Scattering ◽  
Structural Changes ◽  
Md Simulations ◽  
Cellulose Microfibrils ◽  
Dynamic Vapor Sorption ◽  
Time Resolved ◽  
Constant Rate

Abstract Structural changes of cellulose microfibrils and microfibril bundles in unmodified spruce cell wall due to drying in air were investigated using time-resolved small-angle neutron scattering (SANS). The scattering analysis was supported with dynamic vapor sorption (DVS) measurements to quantify the macroscopic drying kinetics. Molecular dynamics (MD) simulations were carried out to aid in understanding the molecular-level wood-water interactions during drying. Both SANS experiments and simulations support the notion that individual cellulose microfibrils remain relatively unaffected by drying. There is, however, a significant decrease in fibril-to-fibril distances in microfibril bundles. Both scattering and DVS experiments showed two distinct drying regions: constant-rate drying and falling-rate drying. This was also supported by the MD simulation results. The shrinking of the fibril bundles starts at the boundary of these two regions, which is accompanied by a strong decrease in the diffusivity of water in between the microfibrils. Graphic abstract

scholarly journals Molecular Dynamics Simulations of Dislocations in TlBr Crystals under an Electrical Field

MRS Advances ◽  
2016 ◽  
Vol 1 (35) ◽  
pp. 2459-2464 ◽  
Author(s):  
X. W. Zhou ◽  
M. E. Foster ◽  
P. Yang ◽  
F. P. Doty
Keyword(s):  
Molecular Dynamics ◽  
Structural Changes ◽  
Vacancy Concentration ◽  
Radiation Detection ◽  
Md Simulations ◽  
Electrical Field ◽  
Electrical Fields ◽  
Charge Model ◽  
Aging Mechanisms ◽  
Dynamics Simulations

ABSTRACTTlBr crystals have superior radiation detection properties; however, their properties degrade in the range of hours to weeks when an operating electrical field is applied. To account for this rapid degradation using the widely-accepted vacancy migration mechanism, the vacancy concentration must be orders of magnitude higher than any conventional estimates. The present work has incorporated a new analytical variable charge model in molecular dynamics (MD) simulations to examine the structural changes of materials under electrical fields. Our simulations indicate that dislocations in TlBr move under electrical fields. This discovery can lead to new understanding of TlBr aging mechanisms under external fields.

scholarly journals Molecular Dynamics Simulations of Mitochondrial Uncoupling Protein 2

2021 ◽  
Vol 22 (3) ◽  
pp. 1214
Author(s):  
Sanja Škulj ◽  
Zlatko Brkljača ◽  
Jürgen Kreiter ◽  
Elena E. Pohl ◽  
Mario Vazdar
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Proton Transport ◽  
Uncoupling Protein ◽  
Homology Modelling ◽  
Md Simulations ◽  
Phospholipid Bilayer ◽  
Mitochondrial Membranes ◽  
Fatty Acid Binding ◽  
Dynamics Simulations

Molecular dynamics (MD) simulations of uncoupling proteins (UCP), a class of transmembrane proteins relevant for proton transport across inner mitochondrial membranes, represent a complicated task due to the lack of available structural data. In this work, we use a combination of homology modelling and subsequent microsecond molecular dynamics simulations of UCP2 in the DOPC phospholipid bilayer, starting from the structure of the mitochondrial ATP/ADP carrier (ANT) as a template. We show that this protocol leads to a structure that is impermeable to water, in contrast to MD simulations of UCP2 structures based on the experimental NMR structure. We also show that ATP binding in the UCP2 cavity is tight in the homology modelled structure of UCP2 in agreement with experimental observations. Finally, we corroborate our results with conductance measurements in model membranes, which further suggest that the UCP2 structure modeled from ANT protein possesses additional key functional elements, such as a fatty acid-binding site at the R60 region of the protein, directly related to the proton transport mechanism across inner mitochondrial membranes.

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